Mitogen activated protein kinase phosphatase-3 (MKP-3) is a dual specificity phosphatase that has a central role regulating intracellular signal transduction by controlling the phosphorylation status of mitogen activated protein kinases. There is considerable evidence indicating MKP-3 could be a potential molecular target for several human diseases. Nonetheless, no potent or selective small molecule inhibitors of this protein phosphatase have been identified. Cell-based chemical complementation assays provide a novel platform technology to screen for cell-active inhibitors of this protein phosphatase. This proposal will provide sufficient reagents, including cells and DMA transfection vectors, to permit the high throughput screening of 100,000 compounds. [unreadable] [unreadable]